AIDS TREATMENT NEWS Issue # 185, 10/15/93
phone 800/TREAT-1-2, or 415/255-05888
CONTENTS:
Vaccine Controversies at San Francisco Conference
Vaccine (gp160) Controversy Update
Flu Season Warning
Vitamin A Deficiency Associated with Increased Death Rate
Antisense: "GEM 91" Human Trial Started in France
Announcements: Recent Clinical Trials Recruiting
HIV: Alpha Interferon, T-Helper Above 500
HIV: ddI Plus d4T Combination, T-Helper 200-500, No Prior
Antiretrovirals
HIV: Nevirapine+AZT, T-Helper 200-500, 4-12 Months Prior
AZT
HIV: ddC Plus AZT, T-Helper Count 100-500, No Prior
Antiretrovirals
Kaposi's Sarcoma: Recombinant Platelet Factor 4 (rPF4),
San Francisco Only
Kaposi's Sarcoma: Pentoxifylline
Announcements
San Francisco: Senator Wellstone Speaks on Single Payer
Health Care Reform
California: "Day of the Dead" Political Funeral,
Sacramento, October 29.
In Memoriam: Andrew Zysman, M.D.
***** Vaccine Controversies at San Francisco Conference
by Dave Gilden
The First International Conference on Engineered Vaccines for
Cancer and AIDS, which was held in San Francisco at the
beginning of the month, was a study in contrasts. On the one
hand, increasing skills in genetic engineering allow complex
manipulations of micro-organisms that result in a wide array
of immune-stimulating products. On the other, there was no
agreement on how to choose the promising HIV-vaccine
strategies from among this wide array. Both types of anti-HIV
vaccines, preventive and therapeutic, were under
consideration. A preventive vaccine would protect people from
becoming infected, whereas a therapeutic vaccine would
enhance the immune response of those who already are living
with HIV.
The disagreements did not prevent polio vaccine discoverer
Jonas Salk, M.D., from delivering an impassioned plea for
rapid steps forward. Addressing representatives of the
various vaccine developers gathered for a panel discussion,
Salk said, "We risk investigating to exhaustionI People in
need are waiting impatientlyI The time has come to move
forward. We need to decide now to do something
cooperatively."
Salk appeared with a group from the Immune Response
Corporation of San Diego, which is investigating his
therapeutic vaccine concept, which involves inoculating with
virus particles that have been both killed and stripped of
their outer coat. The idea is to stimulate an immune response
to HIV's inner protein appearing on the surface of HIV-
infected cells. This therapeutic vaccine has been in human
trials since 1987.
The notion of a therapeutic vaccine has always been saddled
with doubts. Unfortunately, Salk's presentation of his data
early in the conference was not clear-cut enough to dispel
those doubts and demonstrate that we have "enough clues and
indications to go forward," as he put it.
In the hallways, Salk privately commented to us that his talk
at the conference was, in part, an attempt to reverse the
poor impression his associates made earlier this year at
Berlin's Ninth International Conference on AIDS.
Once again, though, obscure slides slipped by one after
another, purporting to show that the "responders" to the
vaccine did better than the "nonresponders." Responders are
defined as those who develop skin reactions when HIV proteins
are applied in a manner similar to a TB skin test. The
percent responding seems to increase with higher doses of
inoculant. Responders fared better than nonresponders, in
that they had slightly higher CD4 levels, fewer clinical
symptoms, slight weight increases, and, for some people,
reduced HIV levels in the blood.
When asked by this writer if his slides were available in
some form that allowed more thorough review, Dr. Salk
demurred, saying the data were very preliminary. The doctor
then grew philosophical: "But this is just information. What
is important is the knowledge. Tell your readers that the
knowledge is there. We know how to make an effective
vaccine."
Is that knowledge really there? Another conference speaker,
Robert Schooley, M.D., of the University of Colorado,
reviewed the state of research on therapeutic vaccines and
made it clear there are still plenty of gaps. "Why should
this approach work?" Schooley asked, noting that the amount
of HIV envelope protein constantly present in the blood is
frequently 100 to 1,000 times greater than the amount in any
vaccine now being injected at periodic intervals during
treatment trials. Vaccine-induced reductions in HIV remain to
be definitely established. Also, it is not known whether HIV
can mutate to escape the protective antibodies engendered by
the vaccine. HIV certainly escapes the defenses the body
naturally sets up against the virus, after all.
Although Salk's colleagues have been testing their vaccine
for six years, they have been unable to resolve such doubts.
Dr. Schooley noted a fundamental problem when comparing
therapeutic vaccine responders to nonresponders, as the Salk
group and other vaccine developers are doing. If responders,
that is those who broaden their anti-HIV immune activity
after vaccination, tend to stay healthier longer than
nonresponders, maybe it is because their immune systems were
superior in the first place. That is what enabled them to be
responders.
The data, therefore, may merely reflect the natural variation
in response to HIV -- some people progress faster than others
to AIDS -- rather than show that the vaccinations produce any
benefit. The controversy over results from Army researchers'
trials of the therapeutic vaccine developed by MicroGeneSys
Corp. of Meriden, CT [see AIDS TREATMENT NEWS #164 and #183]
reflects this uncertainty.
Quick, definitive documentation of a vaccine's benefit
requires an accepted way to evaluate changes in immunity
triggered by vaccines. The lack of consensus continues,
though, for preventive as well as for therapeutic vaccines.
Dr. Salk acknowledged at the conference that "the correlates
of immunity question is holding the effort up. The moment we
have something to measure, the game's over." Trials could
proceed rapidly and decisively by tracking accepted signs of
immune improvement.
Dr. Salk thinks that cell-mediated immunity -- as signified
by his skin test for response to HIV antigens -- is the
appropriate standard (in addition to T-helper cell count,
weight gain, and clinical symptoms). The killer lymphocytes
associated with cell-mediated immunity specialize in
destroying cells infected by virus. Salk thinks that
absolute, complete prevention of HIV transmission from person
to person will not be possible with a vaccine. Rather, cell-
mediated immunity must be primed to immediately isolate the
virus contained within cells and snuff out an incipient
infection. In a sense, preventive and therapeutic vaccines
have a similar role -- controlling HIV after it has already
entered the body -- although the timing of these two vaccines
is different.
But in a presentation at the conference, Susan Zolla-Pazner,
M.D., of New York University indicated that antibodies are
important, too. "Antibodies play a major role in preventing
viral infection," she said. "They play a minor role in
controlling infection."
Dr. Zolla-Pazner's research concerns monoclonal antibodies,
which are laboratory products containing a single specific
antibody. She has found an antibody that seems to neutralize
all the HIV strains common in North America and Europe
(including wild strains, not just laboratory isolates). The
antibody reacts to a section of the V3 loop on HIV's envelope
molecule (gp120). The V3 loop is a part of the virus that is
"out there waving in the breeze," as Dr. Zolla-Pazner
describes it. It is easily accessible to antibody recognition
and attack. Researchers now plan to try out monoclonal
antibodies as a means of preventing HIV transmission during a
few special circumstances -- in babies, to prevent
transmission from HIV-infected mothers at birth, and then in
health care workers exposed to HIV through accidents on the
job. A cocktail of these antibodies may also be useful as a
treatment, Dr. Zolla-Pazner noted.
Another conference participant, Ron Desrosiers, Ph.D.,
described a novel approach to a vaccine for preventing SIV,
the monkey version of HIV. He told AIDS TREATMENT NEWS, "We
tried protecting monkeys from SIV with altered vaccinia virus
plus subunit booster [genetically engineered smallpox-vaccine
virus containing SIV coat proteins plus later inoculations of
pure SIV protein fragments]. It resulted in great antibody
production, but the protection was minimal. So we started out
on a new strategy."
Dr. Desrosiers' new strategy was actually a standard one for
vaccines in other diseases -- a live but weakened, or
attenuated, SIV strain. The SIV was weakened by deleting its
"nef" gene, whose function is poorly understood. The
attenuated virus produced an extremely low-level, benign,
persistent infection instead of a rapidly fatal one. When the
vaccine's effectiveness was tested in four monkeys more than
two years after vaccination, protection was complete against
two closely related SIV strains. Dr. Desrosiers is now
experimenting with SIV strains weakened by removing three to
five minor genes including nef. Last month, his team started
an experiment in chimpanzees using a multiply deleted version
of HIV.
"All the [existing] HIV vaccines have been tested only under
idealized conditions," Dr. Desrosiers said in our interview.
"It's likely they will fail in the field. We need to gather
some basic safety data on our type of vaccine in humans now."
Linda Gritz, Ph.D., of the Therion Biologics Corporation in
Cambridge, MA reports that her company has licensed
Desrosiers' method and is considering doing just that. "But
we hope we don't have to, that one of the other vaccines
we're trying works," she told ATN. "There are tremendous
fears about using a live, attenuated HIV vaccine on
uninfected people. It could take us twenty years to tell
whether we're using a strain of HIV that produces no disease
progression or only slow progression."
Gritz mentioned that Therion is also considering testing a
gene-deleted HIV vaccine for treatment purposes.
Because of all the doubts, Patricia Fast, M.D., Ph.D., who
helps direct AIDS vaccine development at the National
Institutes of Health, told the conference, "It is unlikely we
have the perfect vaccine but we will continue to push on with
every strategy." Her colleague, Dale S. Lawrence, M.D.,
M.P.H., outlined the reasons for moving quickly to efficacy
trials: Vaccines represent an "exquisite weapon" compared to
the "sandbag protection" we now have against HIV.
Lawrence envisions trials requiring thousands of volunteers.
He would be happy to get a 60 percent reduction in HIV
transmission with the present crop of vaccines. For the
vaccine failures (the volunteers who later become infected
with HIV, despite having received the vaccine -- and there
are already rumors of one such failure in a small preliminary
trial of one vaccine), Lawrence foresees a prolonged period
of followup to see whether the vaccine slowed down or
enhanced disease progression.
The community of course desperately needs new forms of HIV
treatment and prevention. Community support will be essential
for the large trials, including the mass testing of
therapeutic vaccines now under consideration by the Army (see
below, and see AIDS TREATMENT NEWS #184). It is also
important not to squander the community's trust by rushing
into mass testing too early, with crudely conceived vaccines
that still resemble "sandbags" more than they do "exquisite
weapons." Loss of public confidence due to the inevitable
failures will make it all the more difficult to test more
promising vaccines in the future.
***** Vaccine (gp160) Controversy Update
by Dave Gilden
The controversy over Army researchers' plans to conduct a
massive trial of therapeutic vaccines (reported in AIDS
TREATMENT NEWS #183) continues on its apparently unstoppable
course, exhausting everyone involved.
The controversy started a year ago when lobbyists hired by
MicroGeneSys Corp. convinced Congress to allocate $20 million
dollars for the Walter Reed Army Institute of Research to
further test the company's therapeutic vaccine. (Therapeutic
vaccines are supposed to strengthen the anti-HIV immune
defenses in people already infected by the virus -- see the
article in this issue on the First International Conference
on Engineered Vaccines for Cancer and AIDS.)
The original appropriation was reviewed by a panel created by
the National Institutes of Health. Nine months ago, this
blue-ribbon panel urged that a multiproduct comparison trial
be carried out, rather than testing a single vaccine alone
(see AIDS TREATMENT NEWS #164, December 4, 1992). But on
September 27, 1993, many of the non-NIH members of the panel
signed a statement arguing that "the scientific evidence to
date does not yet justify Federal support for a large phase
III [efficacy] study of either one or several candidate HIV
therapeutic vaccines." The statement's signers want the $20
million disbursed as a grant program, underwriting a broad
range of AIDS research. Proposals would be judged by an
expert review panel set up by the Department of Defense.
White House AIDS policy coordinator Kristine Gebbie, M.N.,
took a similar position on September 28, in a letter to Rep.
Henry Waxman (D-CA), the chair of the House Subcommittee on
Health and the Environment.
Gregg Gonsalves, of the Treatment Action Group in New York,
reports that spending the $20 million on peer-reviewed,
investigator-initiated AIDS research is also the favored
course of the vast majority of the respondents to a TAG
survey among activists and scientists. (That survey was
published in ATN #183.) He notes that this course does not
preclude a large trial of one or more therapeutic vaccines.
It just makes the Army researchers get in line like everyone
else to justify their proposal.
Back at Walter Reed, Deborah Birx, M.D., has been working
since the spring to get a large comparative trial off the
ground. (The idea of testing the MicroGeneSys vaccine alone
seems to have fallen by the wayside. Her concept is now
similar to that originally floated by the NIH panel.) She has
managed to convince MicroGeneSys to agree to donate its
vaccine on a year to year basis for such a trial, something
the company was previously unwilling to do. Dr. Birx is now
trying to get other therapeutic vaccine developers to
similarly aid the study -- at a cost to the companies of $2
million per year.
Birx envisions conducting a three-year, placebo-controlled
trial with several thousand people per vaccine arm. People
with a wide range of helper T-cell counts would be observed,
and everyone could take whatever other drugs they wanted,
except for experimental antiviral medications.
Dr. Birx contends there are hints that therapeutic vaccines
are useful for treating HIV. But, she told AIDS TREATMENT
NEWS, "Either you buy into this trial as something that
doesn't follow the normal scientific steps orI we'll be
seven years from the answer [of how effective therapeutic
vaccines are] according to usual procedure."
Dr. Birx does have a certain amount of support among
community-based researchers, who would be included in the
trial, and among people with HIV searching for new treatment
options. Interestingly, she is close to her opponents'
position in that she supports a kind of massive roundtable of
scientific and community representatives to reach a consensus
about her project.
A consensus-building process of one sort or another may get a
chance to work if an amendment to the 1994 Defense budget is
passed. That amendment, proposed by Rep. Waxman and now
approved by the House of Representatives, would give the
government another six months to review the need for a large
vaccine trial.
So the saga of the Army's and MicroGeneSys's $20 million
continues to unroll. "We're seeing the best and the worst of
the democratic process," complained Joseph Camarado of Wyeth-
Ayerst Laboratories, MicroGeneSys's corporate backer.
But while arguments re-flared over this $20 million, Congress
on October 5 passed a $227 million increase in AIDS research
funding without any controversy. That money will be
distributed through the National Institutes of Health's
regular grant award process involving independent scientific
review committees.
The NIH process has plenty of critics, but it is still more
orderly than having Congress earmark funds for specific
projects on a political basis. Commented Terry Beswick, who,
at the time of interview, was set to become a temporary
advisor to Kristine Gebbie on research policy, "This is a
lesson in the bad management in science."
Finally, if the groups working on the therapeutic vaccine
trial issue cannot come to an agreement, there is an almost
completely unnoticed measure before Congress to take back the
money. H.R. 1392 (S. 1090 in the Senate) is a general bill to
erase a wide range of mistaken appropriations in last year's
budget. Included in the 3,000 lines of text is a short clause
canceling funding for the large-scale vaccine trial on the
grounds that the proposed trial has not been subject to
competitive bidding.
***** Flu Season Warning
by Dave Gilden
This winter's flu season is likely to be particularly severe,
the U.S. Public Health Service warns. Three to five times the
usual 10,000 to 20,000 flu-related deaths may occur. Worse
yet, the harsh "Beijing" strain of influenza that first
appeared in February mutated at the end of last year's flu
season, and no one is immune to it unless they came down with
flu in April or May.
The U.S. Public Health Service is recommending that all
persons at special risk for flu complications get the updated
version of the flu vaccine by November 15. Among these "at
risk" groups are people with HIV. A poster presentation
(#2249) at Berlin's International Conference on AIDS found
that flu vaccine coverage in the U.S. is "sub optimal," with
only about a third of people with HIV receiving the vaccine.
Also in Berlin, three posters described a low response rate
to the vaccine, especially among people with greatly reduced
helper T-cell counts (posters 500, 1264 and 1276).
Stephen Follansbee, M.D., a San Francisco AIDS specialist who
is following the issue, nevertheless urges anyone with HIV to
be vaccinated. Complications from infection with the
influenza virus include bacterial pneumonia, which can be
fatal. For people with low T-helper cell counts, Dr.
Follansbee suggests that all housemates also have themselves
vaccinated. This would create a kind of sanitary wall around
the person most in danger.
However, those with a history of allergic reactions to flu
shots or to eggs should not be inoculated; and those with
fevers should wait until the fevers subside. The vaccine
consists of killed influenza virus that was grown in egg
cells.
Two posters (209, 1929) in Berlin also dealt with the
question of whether flu vaccination increases the level of
HIV in the body, due to the immune stimulation the inoculant
provokes. Increased HIV replication might spark a further
decline in the immune system.
One of the posters said the vaccine does increase viral load
for several months; the other found no change. To look at the
question further, Dr. Follansbee and a group of associates
are planning a short, 30-person trial involving HIV-infected
volunteers at different helper T-cell counts. HIV levels and
immune function will be measured for 28 days after
vaccination.
The trial is now completely enrolled, and a full analysis of
the data will not be completed until December at the
earliest, well after the recommended vaccination period is
over. But Dr. Follansbee says, "I don't want the study to
undermine people getting shots." Any negative effect of the
flu vaccine is probably minor, compared to the damage the flu
could cause.
***** Vitamin A Deficiency Associated with Increased Death
Rate
A study of HIV-positive intravenous drug users found that
those with a vitamin A deficiency (about 15 percent of the
HIV-positive persons studied) had a death rate several times
as high as those who did not have a vitamin A deficiency.
While this study does not prove that correcting the
deficiency will improve survival, it strongly suggests that
conclusion.
Other studies (unrelated to HIV) have shown that vitamin A
deficiency does impair both cellular and humoral immunity.
Also, vitamin A supplementation in developing countries has
been found to reduce childhood mortality by 20 percent to 54
percent. And vitamin A stores in the body may be reduced by
infection, suggesting that a vicious circle can develop, with
infection depleting vitamin A, and the deficiency causing
more infection.
But on the other hand, recent studies have found that
retinoic acid, which is the active form of vitamin A in the
body, can increase HIV replication in laboratory tests. This
raises the concern that vitamin A supplementation might not
always be helpful in HIV disease. In addition, the
association found in the study does not prove causality,
because patients who were sicker (and more likely to die
anyway) may have therefore developed nutritional
deficiencies, due to malabsorption or other causes.
Reference: Semba RD, Graham NMH, Caiaffa WT, Margolick JB,
Clement L, and Vlahov D. Increased Mortality Associated With
Vitamin A Deficiency During Human Immunodeficiency Virus Type
1 Infection. Archives of Internal Medicine. September 27,
1993; volume 153, pages 2149-2154.
Comment
The studies needed to get definite answers about use of
vitamin A in HIV disease have not been done and may never be
done. In the meantime, people must make decisions on the
information available.
The usual recommendation for vitamin A supplementation is to
use beta carotene, not vitamin A itself. Vitamin A is toxic
in overdose; beta carotene is safer because the body only
converts what it needs to vitamin A. Also, beta carotene is
an antioxidant (vitamin A itself is not), and there are
indications that antioxidants might help to reduce
progression of HIV disease.
The scientifically ideal study would give beta carotene,
and/or vitamin A, to randomly chosen HIV-positive patients
within a study group, then follow them for years to see if
there was a difference in death rate between those who
received the supplementation and those who did not. A more
practical study would use modern tests for viral activity or
viral load, instead of looking for differences in death rate.
This way, results could be obtained in weeks instead of
years, and without serious risk of harming volunteers in the
trial. These results would not give an ultimate answer of
what supplementation is best, but they probably would
establish that certain doses could be used without risk of
increasing HIV activity. Once that is shown, the clear course
of action would be to use the supplements, since there is
overwhelming evidence that vitamin A can reduce the risk of
other infectious diseases, and beta carotene is safe, readily
available, and not expensive.
Meanwhile, it appears that people with HIV should be using at
least some beta carotene (unless their physician recommends
otherwise) to prevent possible vitamin A deficiencies. Even
more importantly, this study re-emphasizes the need for good
overall nutrititional support in AIDS treatment.
***** Antisense: "GEM 91" Human Trial Started in France
The first human trial of an antisense compound for HIV has
started in France. On October 13, Hybridon, Inc. of
Worcester, Massachusetts, announced that it has begun a
single-dose safety study which will test escalating doses of
its compound GEM 91 in up to 24 patients. Hybridon is working
in collaboration with ANRS, the French Agency for AIDS
Research.
In the laboratory, the drug is active against all strains of
HIV which have been tested so far. Resistance is expected to
be less of a problem with antisense compounds than with other
classes of drugs. Animal studies have found that antisense
drugs can work comparably in animals as in the laboratory.
An antisense drug targets specific genetic information in
viruses, other infectious organisms, cancer cells, or human
cells, to prevent one selected gene from working. The drug
targets what is called mRNA (messenger RNA), to prevent the
production of the particular protein which is specified by
the gene.
The importance of antisense is that, once a technology to
make one antisense drug has been developed, other potential
drugs can be designed just by changing the code, as long as
there is a known sequence to be targeted (which is often the
case). Therefore, it may be possible to quickly develop drugs
against a wide variety of diseases. Each drug should be
highly specific against a particular disease, by targeting
sequences which do not normally occur in the body. Therefore,
it should be possible to give effective doses with few side
effects.
An early laboratory study of an antisense compound against
HIV was published in 1986 (see AIDS TREATMENT NEWS #58, June
3, 1988). But developing the basic technology of antisense
has been difficult, since it is necessary not only to code
for specific sequences, but also to do so in a way that can
work as a drug in the body. Now that the technology is
advanced enough for human testing to begin, further progress
may be rapid.
***** Announcements: Recent Clinical Trials Recruiting
Mark Jacobson, M.D., at San Francisco General Hospital,
brought several trials for HIV, and for KS, to our attention.
All but one of these trials is recruiting in several cities
(not only in San Francisco).
None of these trials is listed by the AIDS Clinical Trials
Information Service (at phone number 800/TRIALS-A). This is
because 800/TRIALS-A, a Federally-sponsored service, lists
all Federally-sponsored AIDS trials, but only some privately-
sponsored ones. Trials sponsored by a pharmaceutical company
are only listed if the company agrees, and goes to the
trouble to provide the information.
[When trials are not listed, it can be difficult to find
information by calling the companies directly; it took us
about two days' work to find and confirm the listings below.
One company refused to give us any information, even the
names of the cities where the trial would take place, until
they had authorization from the investigators at the sites,
which would take them ten working days; we got the
information elsewhere. Most gave us the information, but
usually it took a number of calls to find it, even when we
started with a number given out for that purpose. And
sometimes the sponsors give different contact numbers than
the sites themselves. Only a few companies have, coherently
and in one place, all the information potential volunteers
will need to find a trial site near them (if there is one).
Since recruiting volunteers is the biggest problem for most
clinical trials, anyone conducting a trial should at least
pay attention to making it easy to find.]
Note: Not all of the entry criteria for these trials are
listed below. Clinical trials often have many
inclusion/exclusion criteria, most of which apply only to a
few patients. The notices below only list the requirements
which are most likely to exclude potential volunteers, so
that readers can get a quick idea of whether or not they
might qualify.
** HIV: Alpha Interferon, T-Helper Above 500
This trial is studying whether low or moderate doses of alpha
interferon can slow HIV progression in early infection. The
theory behind the trial is that there are two kinds of T-
helper immune response, Th1 (cellular immunity, with cells
attacking and destroying infected cells) and Th2 (which leads
to production of antibodies). For HIV, the Th1 response seems
to be most important; and the Th2 response, when it occurs,
may reduce the Th1 response. Alpha interferon may increase
Th1 activity and/or decrease Th2 activity. If these theories
are correct, it might help to prevent progression of HIV
disease. (AIDS TREATMENT NEWS published an advance notice of
this potentially important trial in issue #179, July 23,
1993.)
Alpha interferon has been used as a treatment in HIV disease
since early in the epidemic, but has not been systematically
studied in early infection. There is reason to believe that
early use might be most beneficial, since without treatment
the Th1 response is lost before a major decline in T-helper
cell count occurs.
Volunteers must be HIV positive, with T-helper count over
500, and must never have used AZT or other antiretrovirals.
They will be tested and must be deficient in one or more of
three measures of Th1 response (recall antigens,
alloantigens, or PHA) -- apparently so that the trial will
have some way to measure treatment success. There are a
number of other inclusion/exclusion criteria.
Those accepted will be randomly assigned to one of three
groups: 0.2 million units of interferon (Intron A) three
times a week, 2.0 million units three times a week, or an
untreated control group. The drug is given by subcutaneous
injection. The treatment will be continued for 12 weeks, and
there will be two later followup visits. This trial is
sponsored by Schering Corporation.
The sites are: Denver (University of Colorado, contact
Virginia Waite, B.S.N., 303/270-8340; the trial should begin
at the Denver site within the next few weeks); Durham (Duke
University, contact Robert Dodge, R.N., 919/684-5260); and
San Francisco (San Francisco General Hospital, contact Linda
Johnson, R.N., 415/476-9296 x84099).
Comment
Alpha interferon is an approved drug, and any physician can
prescribe it. The doses being tested in this trial are low to
moderate. The disadvantage of using the drug outside of the
trial is that until the study is done, nobody knows if this
treatment will be useful. Also, the drug is expensive, and
does have side effects.
** HIV: ddI Plus d4T Combination, T-Helper 200-500, No Prior
Antiretrovirals
This trial, sponsored by Bristol-Myers Squibb, will test five
different combination regimens of two anti-HIV drugs: ddI
(didanosine), which is approved; and d4T (stavudine), which
is in late stages of human testing and also currently in use
through parallel track. This study will look first at the
safety of the combination, since both drugs can cause
peripheral neuropathy. But it will also measure antiviral
activity using a number of tests: acid-dissociated p24
antigen, beta-2 microglobulin, PBMC viral titers, and HIV RNA
and DNA PCR. Development of resistant viruses will also be
measured.
Volunteers must have T-helper counts from 200-500, and must
never have received AZT, ddI, ddC, or d4T. This is a pilot
study, which will only enroll a total of 75 volunteers.
This study will require approximately 12 visits to the clinic
over a period of one year.
The four study sites are: Galveston (the University of Texas,
contact Bernadette Montgomery, 409/772-3991); Los Angeles
(UCLA, contact Suzette Chafey, 310/206-6414); New York
(Cornell Medical Center, contact Jim Mahoney, 212/746-4177);
and San Francisco (San Francisco General Hospital, contact
Ted Bush, R.N., 415/476-9296 ext. 84098).
** HIV: Nevirapine+AZT, T-Helper 200-500, 4-12 Months Prior
AZT
This study will compare the combination of AZT plus
nevirapine (formerly called BI-RG-587) with AZT alone, to see
if the combination can reduce viral measures (HIV RNA, and
viral cultures) and increase T-helper cell count and T-helper
cell percent, after three and six months of treatment. All
patients will continue on AZT throughout the study; and those
initially assigned to placebo will be switched to open-label
nevirapine during the trial.
Volunteers must have T-helper counts of 200-500, and must
have used AZT for at least four months, and no more than 12
months, immediately before entering the study. They cannot
have CDC-defined AIDS, and also cannot have certain HIV-
related conditions.
This trial will be conducted in five cities: Baltimore (Johns
Hopkins University Hospital, contact Becky Becker, R.N., or
Louis Grue, R.N., 410/955-2898); Chicago (Northwestern
University Medical School, contact Pam Donath, R.N., 312/908-
9636); Galveston (University of Texas Medical Branch, contact
Bernadette Montgomery, R.N., 409/772-0361); San Francisco
(San Francisco General Hospital, contact Kathy Dybeck, R.N.,
415/476-9296 x84097); and St. Louis (Washington University
School of Medicine, contact Mark Myers, 314/454-0058). The
trial is sponsored by Boehringer Ingelheim
** HIV: ddC Plus AZT, T-Helper Count 100-500, No Prior
Antiretrovirals
This large study, enrolling over 500 patients at over 20
sites, is comparing different doses and schedules of AZT and
ddC used in combination. There is no placebo, and all
volunteers enrolled will get both drugs. The AZT doses are
500 mg per day (100 mg every four hours while awake) vs. 600
mg per day (200 mg every 8 hours); the ddC doses are 0.75 mg
every eight hours, and 0.375 mg every eight hours. This trial
is sponsored by Hoffmann-La Roche.
Volunteers must have a T-helper count between 100 and 500,
and not have had any previous treatment with AZT, ddI, ddC,
or d4T. They also must not have symptoms of peripheral
neuropathy at the time of the trial, or any history of
peripheral neuropathy of grade 2 or greater.
This trial is being conducted at sites in the following
cities: Albuquerque, Boston, Bronx, Brooklyn, Chicago, St.
Louis, Columbus, Dallas, Denver, Galveston, Harbor City, CA,
Miami (2 sites), Milwaukee, New York, Portland, OR, San
Diego, San Francisco, St. Paul, Washington (2 sites), and
Wichita. For more information about volunteering, call
800/526-6367 teleprompt 2 to be referred to a site near you.
** Kaposi's Sarcoma: Recombinant Platelet Factor 4 (rPF4),
San Francisco Only
This phase I/II trial, sponsored by Repligen, is being
conducted only at San Francisco General Hospital. In a
previous study, shrinkage of KS lesions was found in six out
of 12 patients who were treated with rPF4 by direct injection
into the lesions. This new trial will test the drug for
systemic treatment, giving it in six-hour intravenous
infusions. The trial is looking for evidence of safety, and
also for activity of the drug on KS, either on the skin or
internally.
Volunteers must have biopsy-proven KS, and be clinically
stable.
For more information, contact Carol Arri, R.N., 415/476-9296,
ext. 84094.
** Kaposi's Sarcoma: Pentoxifylline
There are theoretical reasons to believe that pentoxifylline
(Trental), an approved drug, might have some activity against
KS. This trial, sponsored by Hoechst-Roussel, is to make sure
it is safe to combine pentoxifylline with antiretroviral
drugs patients are already using, and to look for evidence of
clinical activity of pentoxifylline, either against KS, or
against the progression of HIV infection itself. [For
background on pentoxifylline as a possible HIV treatment (not
focused on KS), see AIDS TREATMENT NEWS # 156, August 7,
1992.] Nausea has been the most common side effect found so
far.
To enroll in this trial, volunteers must have relatively mild
KS, not be likely to need chemotherapy during the study, and
have had no KS treatment during the last 30 days. There are
separate slots for persons with T-helper counts over 200 and
under 200; the latter are almost full, at least at the San
Francisco site, so it may be easier for persons with over 200
to enroll.
The trial will be conducted at three sites in two cities: Los
Angeles (UCLA, contact Ashley at the Care Facility, 310/206-
6414); Los Angeles (Norris Cancer Hospital, contact their
clinical-trials information office, 800/5-CANCER); and San
Francisco (San Francisco General Hospital, contact Julie
Russell, R.N., 415/476-9296 ext. 84100).
***** Announcements
** San Francisco: Senator Wellstone, Oct. 24, Single Payer
Healthcare Reform
Senator Paul Wellstone (D., Minnesota), principle author in
the Senate of the American Health Security Act of 1993, for a
Canadian style single payer health care reform -- a leading
alternative to the Clinton reform plan -- will address a
rally on Sunday, October 24, 1:30 to 2:30 p.m., at the
Cathedral Hill Hotel in San Francisco. There is no charge for
this event, which is part of a one-day conference by UHCAN!
(Universal Health Care Action Network), an organization
mobilizing grassroots support for single-payer health care
reform. (For more information about the conference, call
UHCAN! at 216/241-8422 or 800/634-4442; or call Neighbor to
Neighbor at 415/824-3355. Registration for the day is $15
without lunch, $30 with lunch).
Senator Wellstone will also address a fundraising reception
later that day in San Francisco; suggested contribution for
this event is $50 to $100, with no contributions over $100
accepted. The reception will be in the Monterey Room of the
Sir Francis Drake Hotel, 450 Powell Street, 5:00 to 7:00 p.m.
For more information about single-payer health care reform,
call Ellen Shaffer in Senator Wellstone's office, 202/224-
5641.
** California: "Day of the Dead" Political Funeral,
Sacramento, October 29.
A political funeral/demonstration against inadequate AIDS
funding in California is being organized by ACT UP chapters
in California. The main event will occur Friday October 29 at
noon at the State Capitol. State AIDS programs have remained
flat or decreased, while the case load has continued to grow.
"The demonstration is planned in conjunction with Halloween
and the Day of the Dead, and will target the State AIDS
budget disaster. ACT UP plans on marching through Sacramento
and eulogizing people who have died of AIDS at the State
Capitol steps. Ghoulish costumes and visuals are encouraged.
"Additionally, if you would like to memorialize a person with
enlarged photographs, or by bringing their ashes to the
demonstration, we will arrange that. Please call 415/252-9200
for more information." [Note: There are legal concerns about
human ashes that need to be considered.]
"We are also planning transportation. If you need a ride
(from San Francisco) to Sacramento, meet at the Safeway on
Market Street in the Castro at 8:30 a.m. on Friday, October
29."
"The political funeral is the first of its kind in Sacramento
and is being organized by a newly formed coalition of
California ACT UP chapters. ACT UP/Golden Gate, ACT UP/San
Francisco, ACT UP/East Bay, ACT UP/Sacramento, ACT UP/San
Diego, and ACT UP/Los Angeles are the participating chapters.
AIDS and health care advocates are involved and endorsing
this action."
[Note: Shortly before we went to press, the official name of
the demonstration was changed to "Bring Out Your Dead," at
the request of ACT UP/San Francisco, which feared that the
original name might be offensive to some who observed the
traditional Day of the Dead.]
For more information, call 415/252-9200.
Background: Day of the Dead
The Day of the Dead is a traditional Mexican holiday with
roots going back before the Spanish conquest. It is a
playful, festive occasion with food and costumes in honor of
the dead. People visit cemeteries on November 1 with
offerings for the departed, wait for the spirits of the dead
to visit them, which happens at midnight, and then leave at
daybreak.
In the U.S., the Day of the Dead has been observed in
different forms since 1972, when it was introduced as a
healing celebration following the East Los Angeles riots;
more recently it has come to the attention of communities
affected by AIDS. In San Francisco this year, there will be a
reception at the Mission Cultural Center on Tuesday, November
2, from 5:00 to 8:00 p.m., then a procession starting at 7:30
p.m. near 24th and Mission.
***** In Memoriam: Andrew Zysman, M.D.
by John S. James
San Francisco activist Andrew S. Zysman, M.D., died of AIDS
complications on October 12. He was 38.
We knew Andy's work through the ACT UP/Golden Gate Treatment
Issues Committee. He focused on research on new treatments
for Kaposi's sarcoma, making many trips to Washington to
bring together government and corporate scientists and
officials so that important trials could proceed.
Andy noticed that Japanese companies, with almost no
experience with the U.S. drug-approval system, often teamed
up with consultants who had plenty of experience in how the
FDA worked five or ten years ago. When mistakes were made,
research stopped; the system has no mechanism to identify
these problems and overcome them. Andy provided relevant
advice, which was often followed. In at least one case, he
made important contributions to involving the U.S. National
Cancer Institute, which has plenty of FDA experience, in a
critical drug development effort, after corporate-FDA
communication had bogged down.
Scientists and officials relied on Andy and other treatment
activists, who -- like bees pollinating flowers -- carried
important messages between them when egos and organizational
constraints prevented direct communication.
Andy was also a leader on other AIDS issues, including
getting an annual price cap on acyclovir to protect those who
must use large, ongoing doses. As a member of the governing
board of the American Association of Physicians for Human
Rights, he testified before the Centers for Disease Control
and helped to prevent mandatory testing (and de facto
dismissal) of HIV-positive healthcare workers.
A memorial service will be held in San Francisco in mid
November. For more information, call 415/552-1428.
***** AIDS TREATMENT NEWS
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Editor and Publisher:
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AIDS TREATMENT NEWS reports on experimental and
standard treatments, especially those available now. We
interview physicians, scientists, other health
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collect information from meetings and conferences,
medical journals, and computer databases. Long-term
survivors have usually tried many different treatments,
and found combinations which work for them. AIDS
Treatment News does not recommend particular
therapies, but seeks to increase the options available.
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ISSN # 1052-4207
Copyright 1993 by John S. James. Permission granted for
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